Helicobacter pylori is an important human pathogen which causes chronic, active inflammation of the stomach (gastritis), and is probably a major predisposing cause of gastric and duodenal ulcers (peptic ulcer disease). This bacterium was first cultured and identified in 1982. Previously called Campylobacter pyloridis and Campylobacter pylori, the bacterium was placed in a new genus and named Helicobacter pylori in 1989; see Goodwin, C. S., J. A. Armstrong, T. Chilvers, M. Peters, M. D. Collins, L. Sly, W. McConnell & W. E. S. Harper, "Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov. and Helicobacter mustelae comb. nov., Respectively", International Journal of Systematic Bacteriology, Vol. 39, No. 4 (Oct. 1989), pp. 397-405. References which disclose adherence characteristics of H. pylori to certain cells include Evans, D. G., D. J. Evans, Jr., J. J. Moulds & D. Y. Graham, "N-Acetylneuraminyllactose-Binding Fibrillar Hemag glutinin of Campylobacter pylori: a Putative Colonization Factor Antigen", Infection and Immunity. Vol. 56, No. 11 (Nov. 1988), pp. 2896-2906; and Evans, D. G., D. J. Evans, Jr. & D. Y. Graham, "Receptor-Mediated Adherence of Campylobacter pylori to Mouse Y-1 Adrenal Cell Monolayers", Infection and Immunity, Vol 57, No. 8 (Aug. 1989), pp. 2272-2278.
A general review of sulfated glyceroglucolipids and related compounds is found in Slomiany, B. L. & A. Slomiany, "Lipids of Mucous Secretions of the Alimentary Tract", Attachment of Organisms to the Gut Mucosa, Boedeker, ed., Vol. II (1984), CRC Press, pp. 24-31. Certain sulfated glyceroglucolipids have been isolated from a lipid extract of human gastric content as reported in Slomiany, B. L., A. Slomiany & G. B. J. Glass, "Glycolipids of the Human Gastric Content", European Journal of Biochemistry. Vol. 78 (1977), pp. 33-39. A general review of the glycoglycerolipid class of molecules is provided in Ishizuka, I., T. Yamakawa, "Glycoglycerolipids", New Comprehensive Biochemistry, Vol. 10 (1985), pp. 101-197. This review covers the occurrence and properties of this class of molecules.
The synthesis of a trisaccharide sulfated glyceroglucolipid homologue has been reported in Ogawa, T., T. Horisaki, "Synthesis of 2-O-hexadecanpyl-1-O-hexadecyl-[.alpha.-Glc-6SO.sub.3 Na-(1-6)-.alpha.-Glc(1-6)-.alpha.-Glc-(1-3)]-sn-glycerol: a proposed structure for the glyceroglucolipids of human gastric secretion and of the mucous barrier of the rat-stomach antrum", Carbohydrate Research. Vol. 123 (1983), pp. C1-C4. The synthesis of a sulfated glycerogalactolipid has been reported in Gigg, R., "The Allyl Ether as a Protecting Group in Carbohydrate Chemistry. Part 10. Synthesis of 3-O-(.beta.-D-galactopyranosyl-3-sulfate)-2-O-hexadecanpyl-1-O-hexadecyl-L -glycerol, `Seminolipid`", Journal of the Chemical Society, Perkin Transactions 1, No. 3 (1979), pp. 712-718. Other sulfur containing glycolipids are reviewed in Gigg, R., "Studies on the Synthesis of Sulfur-Containing Glycolipids", Carbohydrate Sulfates, American Chemical Society Symposium Series, Vol. 77 (1978), pp. 44-66. This volume also reviews a variety of other types of carbohydrate sulfates and describes their properties and uses.
The adherence of H. pylori to triglucosyl monoalkylmonoacylglycerol sulfate is disclosed in Slomiany, B. L., J. Piotrowski, A. Samanta. K. VanHorn, V. L. N. Murty & A. Slomiany, "Campylobacter pylori Colonization Factor Shows Specificity for Lactosylceramide Sulfate and GM3 Ganglioside", Biochemistry International, Vol. 19, No. 4 (October, 1989), pp. 929-936. The adherence of H. pylori to a sulfated alkylacyl glycerolipid is reported in Lingwood, C. A., H. Law, A. Pellizzari, P. Sherman & B. Drumm, "Gastric Glycerolipid as a Receptor for Campylobacter pylori", The Lancet. Jul. 29, 1989, pp. 238-241.
It is an object of the subject invention to provide novel methods for treating or preventing gastroduodenal diseases or disorders caused or mediated by H. pylori, such as gastritis and peptic ulcer disease.